title: Cornichons control ER export of AMPA receptors to regulate synaptic excitability.
abstract: The strength of synaptic communication at central synapses depends on the number of ionotropic glutamate receptors, particularly the class gated by the agonist AMPA (AMPARs). Cornichon proteins, evolutionarily conserved endoplasmic reticulum cargo adaptors, modify the properties of vertebrate AMPARs when coexpressed in heterologous cells. However, the contribution of cornichons to behavior and in vivo nervous system function has yet to be determined. Here, we take a genetic approach to these questions by studying CNI-1--the sole cornichon homolog in C. elegans. cni-1 mutants hyperreverse, a phenotype associated with increased glutamatergic synaptic transmission. Consistent with this behavior, we find larger glutamate-gated currents in cni-1 mutants with a corresponding increase in AMPAR number. Furthermore, we observe opposite phenotypes in transgenic worms that overexpress CNI-1 or vertebrate homologs. In reconstitution studies, we provide support for an evolutionarily conserved role for cornichons in regulating the export of vertebrate and invertebrate AMPARs.
authors.affiliation: Department of Biology, University of Utah, Salt Lake City, UT 84112-0840, USA.
authors.forename: Penelope J
authors.initials: PJ
authors.lastname: Brockie
authors.forename: Michael
authors.initials: M
authors.lastname: Jensen
authors.forename: Jerry E
authors.initials: JE
authors.lastname: Mellem
authors.forename: Erica
authors.initials: E
authors.lastname: Jensen
authors.forename: Tokiwa
authors.initials: T
authors.lastname: Yamasaki
authors.forename: Rui
authors.initials: R
authors.lastname: Wang
authors.forename: Dane
authors.initials: D
authors.lastname: Maxfield
authors.forename: Colin
authors.initials: C
authors.lastname: Thacker
authors.forename: Frédéric
authors.initials: F
authors.lastname: Hoerndli
authors.forename: Patrick J
authors.initials: PJ
authors.lastname: Dunn
authors.forename: Susumu
authors.initials: S
authors.lastname: Tomita
authors.forename: David M
authors.initials: DM
authors.lastname: Madsen
authors.forename: Andres V
authors.initials: AV
authors.lastname: Maricq
mesh_terms: D000818:Animals; D017173:Caenorhabditis elegans / Q000378:metabolism*; D002478:Cells, Cultured; D004721:Endoplasmic Reticulum / Q000378:metabolism*; D018698:Glutamic Acid / Q000378:metabolism; D008565:Membrane Proteins / Q000378:metabolism*; D009154:Mutation / Q000235:genetics; D009474:Neurons / Q000166:cytology / Q000378:metabolism; D021381:Protein Transport / Q000502:physiology; D018091:Receptors, AMPA / Q000819:agonists / Q000235:genetics / Q000378:metabolism*; D013569:Synapses / Q000378:metabolism*; D009435:Synaptic Transmission / Q000502:physiology*; D018350:alpha-Amino-3-hydroxy-5-methyl-4-isoxazolepropionic Acid / Q000378:metabolism
chemical_list: D008565:Membrane Proteins; D018091:Receptors, AMPA; D018698:Glutamic Acid; D018350:alpha-Amino-3-hydroxy-5-methyl-4-isoxazolepropionic Acid